Impaired wound healing is an unfortunate consequence of diabetes. It is also seen in the elderly, as well as individuals taking steroid medication. There is an urgent need for a therapy that will be safe, effective, and easy to apply to improve impaired wound healing. The situation is most urgent for individuals with diabetes, whose foot ulcers are the most frequent cause for lower extremity amputations in the United States. This project will lead initially to the marketing of a treatment modality that will promote healing of diabetic foot ulcers. It will be used for recalcitrant ulcers where healing is not progressing. It can be used for other difficult wounds as well. There is no effective treatment for such wounds at this time. Our goal for this SBIR is to develop a novel robust transfection strategy using iontophoresis. We have preliminary work showing that this can be effective. Iontophoresis is performed using a low voltage to create an electrical current in tissue. In our situation the negatively charged plasmid DNA is driven through the tissue from the anode to the cathode. For Phase 1 of this SBIR we will work with a group from Johns Hopkins University, School of Bioengineering, to optimize the electrode arrays and electrical parameters to achieve transfection suitable for improving wound healing. In Phase 2 we will assess the efficacy and safety of the approach in a porcine model. Our group has shown that the transcription factor Hypoxia Inducible Factor- 1 (HIF-1) can improve wound healing. DNA delivery of a peptide like HIF- 1 is necessary because simple application of peptide growth factors has not been effective because of poor absorption, and because the peptides are rapidly destroyed by peptidases in the dermis. The DNA plasmid delivery promotes continuous production of the peptide in the dermis to circumvent these delivery problems.